Polymeric compositions have been used as surface coatings in medical applications, anti-fog applications and ink-absorbing (or printing) applications. However, the known compositions may be improved or have drawbacks discussed below.
A variety of polymers have been used as coatings for medical devices, e.g. polyethylene oxide (PEO), polyethylene glycol (PEG), polyvinyl pyrrolidone (PVP), polyurethane (PU), polyacrylates and methacrylates (PMA, PHEMA etc). Each of the polymeric types mentioned are hydrophilic polymers alone, and as such, are water soluble and will not form durable coatings unless bonded or somehow restrained at the surfaces. The incorporation of binder resins, or copolymer modifications to minimize the water solubility improves durability of these coatings.
Accordingly, polyvinyl pyrrolidone (PVP) has been suggested for use as a medical device coating alone or in combination with other polymers. For example, polyvinyl pyrrolidone may be bonded to a substrate by thermally activated free radical initiators, UV light activated free-radical initiators, or E-beam radiation. One disadvantage of using such coatings is that high energy radiation such as E-beam radiation can be deleterious to some of the materials used in medical devices and is restricted to “line-of-sight” cure as the radiation must contact the coating and its initiator molecules in order to provide for polymerization to occur.
PVP is generally used in solvent and/or water based formulations in combination with other polymers. One such coating is made from a copolymer of PVP and glycidyl acrylate. This coating relies on the presence of amino groups on the surface of the substrate to react with the epoxy groups of the glycidyl acrylate to covalently bond the PVP-containing copolymer to the substrate. Many substrates, including silicone rubber, do not contain any free amino groups, and thus this type of coating cannot form covalent bonds with the surface of the silicone substrate, resulting in poor adhesion. This polymer suffers from the same restrictions as the radiation cured coatings discussed above.
Other suggested coatings are composed of a mixture of PVP and polyurethane. These coatings provide low friction surfaces when wet. One such coating is a polyvinyl pyrrolidone-polyurethane interpolymer with strong hydrogen-bonding between the PVP and the urethane/urea groups. Another such coating is composed of hydrophilic blends of PVP and linear preformed polyurethanes, again relying on the strong hydrogen bonding of the blends. In addition, PVP may be incorporated into a polyurethane network by combining a multifunctional polyisocyanate and a multifunctional polyol with a PVP solution and initiating polymerization of the polyurethane around the PVP. Still another such coating is composed of two layers: a primer and a top coat. The primer coat is a polyurethane prepolymer containing free isocyanate groups, while the top coat is a hydrophilic copolymer of PVP and a polymer having active hydrogen groups, such as acrylamide. The two layers react together to form a robust coating. In each of these coatings, the urethane polymer associated with the PVP determines the properties of the coating and the degree to which there is hydrogen-bonding between the two polymers. Additionally unreacted prepolymer can dissolve into the topcoat destroying the integrity of the primer.
Water-based polyurethane coating compositions can provide medical devices with hydrophilic surfaces. The coatings contain a hydrophilic polymer such as polyvinylpyrrolidone, polyethylene oxide or methylcellulose imbedded in a polyurethane matrix so that the article becomes slippery and lubricious when wet. These polymers have been used in combination with various other materials to produce improved lubricious coatings for devices such as general medical tubing, catheters, guidewires, stents and alike. As for previous polymer blend coatings, the amount of hydrogen bonding determines the durability of the slip.
Improvements over the hydrogen bonding of a urethane matrix to the hydrophilic polymer has been made by using a urethane matrix which contains reactive species such an organic acid or amine. These functions can react with low molecular weight multifunctional crosslinkers such as aziridines, carbodiimides and the like. These multifunctional crosslinkers can have one or two attachment on the polymer in the coating and another attachment, for example, an organic acid available on the substrate surface to provide adequate and improved adhesion to the substrate. This three dimensional matrix allows improved adhesion, as well as a matrix formation that supports and contains the hydrophilic polymer over and above the simple hydrogen bonding mentioned above. Increased durability of the coating's slip which is derived from retained hydrophilic polymers is the result. The network crosslink density must be controlled to allow for slip with durability.
Coatings incorporating PEO and isocyanates have also been suggested. Polyols may be combined with PEO/isocyanate coatings to produce a crosslinked polyurethane network, thereby entrapping the PEO. However, such coatings generally have the same drawbacks as discussed above. The proportion of hydrophilicity, the selection of other polyols and the stoichiometric ratios of isocyanate to polyol, as well as atmospheric conditions and potlife issues can be difficult to control and all impact the successful use of these coatings.
Methods for providing a medical apparatus with a protective surface coating have also been suggested to make the medical apparatus scratch and puncture resistant. The protective coating comprises a polymeric matrix consisting of a water-based urethane, acrylic or epoxy and uses elevated curing temperatures. Plasma or corona pretreatments or the use of a primer is suggested. The polymeric matrix is reinforced by lamellar or fiber-like agents such as micaceous pigments, glass fiber or tungsten powder for higher surface hardness. The coating also comprises polyfunctional aziridine, carbodiimides, urea formaldehyde, melamine formaldehyde, crosslinker condensates, epoxies, isocyanates, titanates, zinc compounds or silanes as crosslinkers. The crosslinkers are added optionally to provide improved hardness, adhesion and chemical and water resistance. The coating further comprises an anti-slip additive or antimicrobials or therapeutic agents.
A multicomponent complex for sustained delivery of bioeffective agents has also been suggested in which the bioeffective agent is anchored by covalent bonds with aziridines, epoxys, formaldehydes or metal esters such as titanates or zircoaluminates to a urethane on a medical device made of steel or urethane. The preferred covalent bonds for a cleavable linkage under hydrolysis reaction are esters. Hydroxy-terminal hydrophilic materials such as polyethylene oxide can be co-reacted to improve hydrophilicity. Alternatively a multilayer polymeric system can be used with up to three layers.
It has also been suggested to achieve slip by mixing urethane with a PTFE, wax, silicone or siloxane emulsion. The carboxylic acid groups of the substrate and coating may then be linked with a cross-linking agent, such as a polyfunctional aziridine. The siloxane emulsion is dispersed in the urethane polymer and “blooms” to the surface, lubricating the surface and replenishing itself from reservoirs in the coating. Fugitive, silicones and waxes can be difficult to contain in manufacturing and will cause problems with other bonding and coating operations when they contaminate the manufacturing areas.
It has been suggested to apply solutions of polyvinylpyrrolidone with isocyanate and/or polyurethane in multi-step operations. However, these coatings often lack good durability. Moreover, it is difficult to control the exact composition of the final coating, because the composition is a complex function of several factors, such as the amounts of each of the coating solutions that happen to deposit on the substrate, the amount of the first coating that happens to react with other material before the top coat is applied, or the amount of the first coating that re-dissolves when the additional coating is applied. Coating composition uniformity of these multi-step coatings is further complicated because, during dip coating, different parts of the same object are likely to see different dwell times and therefore the amount of the first component that re-dissolves is variable. Multiple step coating processes are also more complex and more time, labor, and material intensive. Furthermore, these are usually solvent based.
Many of these coatings have insufficient adhesion to substrates such as silicone, polished stainless steel, PE, PEBAX and the like. Because these coatings do not form linkages with the surface of the substrate, they have poor adherence and durability and are relatively easily rubbed off from the surface when wetted. Even when achieving good wetting of the surface with strong solvents and incorporation of highly reactive functionalities, the adhesion can be less than ideal.
As a result, these coatings often require surface pretreatments and/or priming. Chemical pretreatments such as “tetra etch” for PTFE and corona, plasma or gas/flame pretreatments can successfully create functional groups at the surface that allow for covalent linkage to the reactive materials in the coating. Primers can include materials that react with or bind to the substrate with some functionality to allow wetting and adhesion of a subsequently applied coating. Roughening of the surface can expose polymer without processing aids and increase the mechanical interpenetration with the surface.
Thus there is still a need for coatings for medical applications which can be applied economically, are biocompatible provide improved adhesion to the substrate being coated, e.g. the medical device, improve loading capacity for other (hydrophilic) polymers and additives such as drugs, and improve durability while also providing improved lubricity (or reduced coefficient of friction) when the surface of the coating is contacted with water, blood or body fluids.